Genetic differences may affect vitamin E – cancer relationship

The effects of vitamin E status on the risk of prostate cancer may be modulated by genetic differences in enzymes that control oxidative stress, according to new research.

Writing in the Journal of Nutrition, researchers investigated the associations between serum vitamin E (alpha- and gamma- tocopherols), their effect on oxidative stress regulation, and the risk of prostate cancer.

The researchers, led by Marian Neuhouser from the University of Washington and the Fred Hutchinson Cancer Research Center, found that patients with prostate cancer had lower serum alpha- tocopherol levels than non-cancer controls.

Neuhouser and her colleagues studied the interaction of genetic differences (polymorphisms) in four enzymes, including myeloperoxidase (MPO), with serum alpha- and gamma- tocopherol levels and prostate cancer risk in 18,314 heavy smokers and asbestos-exposed workers.

“Among current smokers, both high serum alpha- and gamma-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer,” said Neuhouser and colleagues.

They added that among current smokers with low serum alpha-tocopherol concentrations, certain MPO genotypes that down-regulate oxidative stress were associated with an increased risk for aggressive prostate cancer.

“Conversely, current smokers with these genotypes who had high alpha-tocopherol concentrations had a reduced risk for aggressive prostate cancer,” they said.

The vitamin E family

Tocotrienols are a form of vitamin E that have traditionally been in the shadow of the more popular vitamin E form – tocopherols.

Overall, there are eight forms of vitamin E: four tocopherols (alpha, beta, gamma, delta) and four tocotrienols (alpha, beta, gamma, delta). Alpha-tocopherol (alpha-Toc) is the main source found in supplements and in the European diet, while gamma-tocopherol (gamma-Toc) is the most common form in the American diet.

Tocotrienols (TCT) are only minor components in plants, although several sources with relatively high levels include palm oil, cereal grains and rice bran.

While most research on vitamin E has focused on alpha-Toc, studies into tocotrienols account for less than one per cent of all research into vitamin E.

From a historical perspective, the ATBC study first showed prostate cancer risk reductions of 32 per cent with vitamin E supplementation in male smokers.

However, two randomized controlled trials, the Physicians’ Health Study II and SELECT trials, then failed to find a protective benefit of vitamin E supplementation on prostate cancer risk.

But, Neuhouser and her team noted that such studies did not consider the potential effect of important genetic polymorphisms on vitamin E metabolism.

Study details

The authors reported that among current smokers, higher serum alpha-tocopherol levels were associated with lower cancer risk, reporting a 34 per cent decrease in cancer risk between highest and lowest groups of vitamin E status.

Genetic variations in the four enzymes were associated with nearly two-fold increase in the risk of aggressive prostate cancer among current smokers with low serum alpha-tocopherol levels, said Neuhouser and her colleagues.

They noted that polymorphisms in genes controlling the enzyme myeloperoxidase may alter aggressive prostate cancer risk.

The researchers found that higher levels of serum alpha-tocopherol may be particularly important among men with certain, high risk, myeloperoxidase genotypes to reduce the risk of prostate cancer.